1. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
2. Department of Pathology, University of Brescia/Spedali Civili di Brescia, Brescia 25123, Italy
3. Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia
4. Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia
5. Department of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts 02115, USA
6. Ludwig Institute for Cancer Research at Memorial Sloan Kettering Cancer Center, New York 10021, USA
7. These authors contributed equally to this work.

Correspondence to: Mark J. Smyth^3,4,7Robert D. Schreiber^1,7 Correspondence and requests for materials should be addressed to R.D.S. (Email: schreiber@immunology.wustl.edu) or M.J.S. (Email: mark.smyth@petermac.org).

The capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes^{1, 2, 3, 4, 5, 6, 7, 8} that function either independently or in sequence⁹: elimination (cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium (expansion of transformed cells is held in check by immunity); and escape (tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected (occult) cancer from organ donor into immunosuppressed recipients¹⁰. Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo. We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods.

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